Interaction of Xiphophorus and murine Fyn with focal adhesion kinase.
The Src family kinase/Focal Adhesion Kinase (FAK) complex is a signaling platform playing a crucial role in transformation downstream of oncogenic growth factor receptors. In the case of melanoma in Xiphophorus fish, the oncogenic EGF receptor orthologue Xiphophorus melanoma receptor kinase (Xmrk) effects continuous activation of the Src family kinase Fyn, but not of the other family members Src or Yes. Here, Fyn is strongly involved in promoting many tumorigenic events. Although Fyn is expressed in most mammalian tissues, there are only few reports of its involvement in the development of solid tumors. To find out whether the prominent role of Xiphophorus Fyn is based on an altered binding to its important binding partner FAK when compared to its mammalian Fyn counterparts, we performed yeast-two-hybrid analyses. We compared Xiphophorus and murine Fyn with respect to their binding to full-length and truncated FAK constructs. We found that interaction with FAK occurs similarly for Xiphophorus and mouse Fyn. Both phosphorylated FAK residue Y397 and FAK proline-rich domain are involved in Fyn binding. We also found interaction of FAK and Fyn in human melanoma cell lines. These data suggest a possible, yet unrecognized role of Fyn in the tumorigenesis of human melanoma, too.
Teutschbein
Janka
J
Physiological Chemistry I, University of Würzburg, Biocenter, Am Hubland, D-97074 Würzburg, Germany.
Schartl
Manfred
M
Meierjohann
Svenja
S
D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003532:Cyprinodontiformes; D029941:Fish Proteins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000473:pathology; D008546:Melanoma, Experimental / Q000201:enzymology; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology; D020798:Two-Hybrid System Techniques; D019061:src-Family Kinases / Q000378:metabolism*
D029941:Fish Proteins; D020794:Receptor Protein-Tyrosine Kinases; C077101:Xmrk protein, Xiphophorus; D051416:Focal Adhesion Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases